In order to enhance tissue regeneration, two growth factors (VEGF and BMP-2) will be presented at a defect site by sequential release from a polymer scaffold. BMP-2 encoding plasmids will be presented by a scaffold containing incorporated VEGF. As the scaffold degrades, VEGF will be released to promote the invasion of new blood vessels into the implant, while BMP-2 plasmids will be transfected by neighboring mesenchymal cells to promote differentiation into osteoblasts and migration of osteoblasts into the implant for improved bone formation. As controlled by scaffold production, VEGF will be released prior to BMP-2 plasmids to allow for the initial vascularization of the implant, which provides transport of nutrients to migrating cells. The expression of BMP-2 will be sufficiently postponed to allow for neovascularization due to scaffold degradation and DNA transfection. In vitro release rates of each growth factor will be examined independently from each scaffold component as well as from the entire construct. The scaffold's ability to promote bone regeneration by sequential release of two growth factors will be examined in a critical defect model of the rat cranium. Vascularization and bone formation will be compared to several control groups. [unreadable] [unreadable]